Purpose: To detect the progression of experimentally induced periapical lesions on periapical radiograph and cone beam computed tomograph (CBCT) by quantitative analysis. Materials and Methods: After the removal of coronal pulps from premolars of two Beagle dogs, the root canals of premolars were exposed to oral environment during one week and then sealed for 70 days. Digital periapical radiographs and CBCTs were taken at baseline and every 7 days for 77 days after pulp exposure. We examined occurrence and areas of periapical bone resorption. Three comparative groups of CBCT radiographs were prepared by average projection of thin slabs with different bucco-lingual thicknesses (0.1, 3.0, and 8.0 mm) using a 3D visualization software. Radiographic densities were compensated by image normalization. Digital images were processed with mathematical morphology operations. The radiographic density and morphological features of periapical lesions were compared among three groups of CBCT in different time points. Results: In the CBCT group with 0.1 mm thickness, radiographic density (p<0.05) and trabecular bone area (p<0.01) were significantly decreased at the fifth week. However, in the CBCT groups with 3 mm and 8 mm thickness and periapical radiographs, none of densitometric and morphological features showed any significant differences in different time points. Radiographic density of periapical lesion showed increasing tendency at the eleventh week after pulp exposure. Conclusion: Radiographic detection of periapical lesions was possible at the fifth week after pulp contamination by quantitative method and was affected by buccolingual bone thickness.